A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV) (CMV)

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ClinicalTrials.gov Identifier: NCT01376778

Recruitment Status :
Active, not recruiting

First Posted : June 20, 2011

Last Update Posted : December 5, 2018

Sponsor:

The George Washington University Biostatistics Center

Collaborator:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Cytomegalovirus (CMV) is a common virus that usually presents with few if any side effects. When first infected, some people may have symptoms similar to mononucleosis (i.e., fatigue, weakness, fever, swollen glands). Most people in the United States are infected during childhood or as adults if they work around children. Pregnant women, who have not been infected with CMV in the past and become infected during pregnancy (i.e. a primary infection), may cause their babies to get infected with CMV. Babies that are infected may develop permanent disabilities including hearing loss and a small portion will die from the infection.

Currently it is not routine practice to screen pregnant women for CMV infection. Additionally, there is no agreement about how to evaluate and manage pregnant women infected with CMV for the first time. There is also no evidence that treatment is beneficial for the baby.

The purpose of this research study is to determine whether treating pregnant women who have a primary CMV infection with CMV antibodies will reduce the number of babies infected with CMV.

Cytomegalovirus (CMV) is the most common congenital infection, with approximately 44,000 congenitally infected infants in the U.S. per year. A substantial proportion of these infants will die or suffer permanent injury as a result of their infection. The severity of congenital infection is greatest with primary maternal CMV infection. Currently, there is no proven method of preventing congenital CMV infection, and the approach to primary maternal CMV infection in the United States is haphazard and ineffective. One small, non-randomized study suggests that maternal administration of CMV hyperimmune globulin may significantly reduce the rate of congenital CMV infection following maternal primary infection. The MFMU CMV Trial will address the primary research question: does maternal administration of CMV hyperimmune globulin lower the rate of congenital CMV infection among the offspring of women who have been diagnosed with primary CMV infection during early pregnancy?

The research study is funded by the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD). Fourteen medical centers across the country are participating in this research study. In all, 800 pregnant women who are identified with a primary CMV infection will be enrolled in this research study. The children of these women will be evaluated and tested at one and two years of age.

The study's active drug is Cytogam® which is an immunoglobulin G (IgG) containing a standardized amount of antibody to CMV. This drug contains pooled adult human plasma selected for high titers of antibody for CMV, and is administered intravenously at a dose of 100 mg/kg body weight.

The primary outcome is defined as fetal loss (spontaneous or termination), confirmed fetal CMV infection from amniocentesis, neonatal death before assessment of CMV infection can be made, or neonatal congenital CMV infection. Neonatal congenital CMV infection is diagnosed by urine or saliva collected by 3 weeks of age that is positive for CMV by culture (the intent will be to obtain in the first two days of life). In the event that Polymerase Chain Reaction (PCR) is positive but culture is negative, a repeat culture must be positive by 3 weeks of age.

Growth restriction defined as <5th percentile weight for gestational age, assessed specifically by sex and race of the infant based on United States birth certificate data

Microcephaly [ Time Frame: 3 days of life ]

Symptomatic CMV infection [ Time Frame: 3 weeks of life ]

Symptomatic CMV infection defined as CMV isolated from an amniocentesis, or urine or saliva during the first three weeks of life and at least one of the following: jaundice, hepatomegaly, splenomegaly, growth restriction, failure to thrive, intracerebral calcifications, microcephaly, hypotonia, seizures, petechial rash, hearing loss, interstitial pneumonitis, thrombocytopenia, anemia, hepatitis, chorioretinitis, or CMV in cerebrospinal fluid

Intraventricular hemorrhage [ Time Frame: 1 day of life ]

Intraventricular hemorrhage (IVH) as determined by cranial ultrasounds performed as part of routine clinical care and classified based on the Papile classification system

Ventriculomegaly [ Time Frame: 1 day of life ]

Retinopathy of prematurity (ROP) [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 4 weeks ]

This diagnosis will be reached when an ophthalmologic examination of the retina has been performed and retinopathy of prematurity (ROP) is diagnosed at Stage I (demarcation line in the retina) or greater.

Respiratory distress syndrome [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 4 weeks ]

Respiratory distress syndrome (RDS) defined as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis), with an oxygen requirement and a chest x-ray that shows hypoventilation and reticulogranular infiltrates.

Chronic lung disease [ Time Frame: 28 days of life ]

Chronic lung disease, or bronchopulmonary dysplasia (BPD) defined as oxygen requirement at 28 days of life.

Necrotizing enterocolitis (NEC) [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 4 weeks ]

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Ages Eligible for Study:

Child, Adult, Older Adult

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Diagnosis of primary maternal CMV infection on the basis of one of the following:

Evidence of maternal seroconversion with development of CMV IgG antibody following a prior negative CMV screen

Gestational age at randomization no later than 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound; or no later than 27 weeks 6 days for women with a positive IgM, negative IgG initially screened before 23 weeks who are rescreened after 2-4 weeks and have evidence of IgG seroconversion.

Singleton pregnancy. A twin pregnancy reduced to singleton (either spontaneously or therapeutically) before 14 weeks by project gestational age is acceptable.

Exclusion Criteria:

Maternal CMV infection pre-dating pregnancy as defined by a high IgG avidity index or a positive IgG in the presence of a negative IgM.